Vitamin D receptor deficiency increases systolic blood pressure by upregulating the renin-angiotensin system and autophagy.

The vitamin D receptor (VDR) may regulate blood pressure via multiple pathways. The present study investigated the underlying mechanism by which deficiency increases blood pressure. A total of 16 8-week-old male littermate mice were randomly divided into the knockout and wild-type groups ( and , respectively). Blood pressure was measured using a four-channel PowerLab data acquisition and ADI software analysis system. After euthanasia, vascular smooth muscle cells (VSMCs) were isolated from the and mice. Oxidative stress, renin-angiotensin system () activation and autophagy markers were measured in the isolated VSMCs using reverse transcription-quantitative PCR (RT-qPCR), western blotting and transmission electron microscopy (TEM) assays. Mean systolic pressure was significantly higher in the mice compared with the mice. RT-qPCR and western blotting analyses indicated that RAS markers (angiotensin II and II type 1 receptor) were significantly upregulated, oxidative stress was increased (evidenced by reduced superoxide dismutase and peroxiredoxin-4) and autophagy was activated (upregulation of autophagy related protein 7, Beclin 1 and microtubule-associated proteins 1A/1B light chain 3A) in the VSMCs compared with the VSMCs. TEM demonstrated that there were more autophagy bodies in the VSMCs compared with the VSMCs. In conclusion, deficiency was associated with high blood pressure. The mechanism underlying the increase in blood pressure caused by deficiency may involve activation of the RAS, as well as increased oxidative stress and autophagy of VSMCs.